Influence of the constitutive, conditional and inducible astroglia-derived tenascin-C ablation on synaptic function

星形胶质细胞来源的腱蛋白-C 的组成型、条件型和诱导型消融对突触功能的影响

• 批准号: 5430089
• 负责人: Professorin Dr. Melitta Schachner
• 金额: --
• 依托单位: Seniorgruppe Biosynthese Neuraler Strukturen
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5430089?language=en
• 关键词: Influence; constitutive; conditional; inducible; astroglia

Extracellular matrix molecules derived from glial cells have been shown to be important mediators of neuron-glia interactions during development. They have recently also been shown to be crucial ingredients in regeneration of the injured nervous system and in synaptic plasticity of adult mammals. One of these extracellular matrix molecules is tenascin-C that is prominently expressed by astrocytes at early stages of brain development and, in some brain regions, also in the adult. The aim of our study is to investigate how tenascin-C may affect synaptic plasticity in the hippocampus of young adult mice. These studies will be conducted with constitutively, conditionally (under the control of the human GFAP promoter) and tamofixen inducibly-ablated mice. The dynamic features of astroglial process and dendritic spine morphology will be studied in these mutants by 2-photon microscopy using transgenic mice expressing green fluorescent protein under the control of the human GFAP promoter and Dil labeling of spines. Conventional immunocytochemistry will be carried out to monitor neurons and subpopulations of neurons and their relative proportions and localization with respect to astrocytes. Electron microscopy will be used to stereologically monitor the fine structure of synapses and associated astrocytic processes. These finings and extensive electrophysiological measurements will be related to CA1 and CA3 hippocampus-associated behavioral parameters, such as trace fear conditioning, pattern completion, working memory and step-down avoidance, representing higher levels of astrocyte-synapse interactions.

来源于神经胶质细胞的细胞外基质分子已被证明是发育过程中神经元-神经胶质相互作用的重要介质。它们最近也被证明是受伤神经系统再生和成年哺乳动物突触可塑性的关键成分。这些细胞外基质分子之一是腱生蛋白-C，其在脑发育的早期阶段由星形胶质细胞显著表达，并且在某些脑区域中，也在成人中表达。本研究的目的是探讨腱生蛋白C如何影响年轻成年小鼠海马的突触可塑性。这些研究将用组成型、条件性（在人GFAP启动子的控制下）和他莫菲生诱导消融的小鼠进行。将使用在人GFAP启动子控制下表达绿色荧光蛋白的转基因小鼠和Dil标记的棘，通过双光子显微镜研究这些突变体中星形胶质细胞过程和树突棘形态的动态特征。将进行常规免疫细胞化学以监测神经元和神经元亚群及其相对于星形胶质细胞的相对比例和定位。电子显微镜将用于体视学监测突触和相关星形胶质细胞过程的精细结构。这些精细和广泛的电生理测量将与CA 1和CA 3脑区相关的行为参数，如微量恐惧条件反射，模式完成，工作记忆和步下回避，代表更高水平的星形胶质细胞-突触相互作用。